PL131222B1 - Process for preparing 4-/2'-nitrophenyl/-2,6-dimethyl-3,5-dicarbomethoxy-1,4-dihydropyridine - Google Patents
Process for preparing 4-/2'-nitrophenyl/-2,6-dimethyl-3,5-dicarbomethoxy-1,4-dihydropyridine Download PDFInfo
- Publication number
- PL131222B1 PL131222B1 PL1982237935A PL23793582A PL131222B1 PL 131222 B1 PL131222 B1 PL 131222B1 PL 1982237935 A PL1982237935 A PL 1982237935A PL 23793582 A PL23793582 A PL 23793582A PL 131222 B1 PL131222 B1 PL 131222B1
- Authority
- PL
- Poland
- Prior art keywords
- dihydropyridine
- nitrophenyl
- dimethyl
- dicarbomethoxy
- nitrobenzaldehyde
- Prior art date
Links
- 238000004519 manufacturing process Methods 0.000 title 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 15
- CMWKITSNTDAEDT-UHFFFAOYSA-N 2-nitrobenzaldehyde Chemical compound [O-][N+](=O)C1=CC=CC=C1C=O CMWKITSNTDAEDT-UHFFFAOYSA-N 0.000 description 11
- 238000000034 method Methods 0.000 description 9
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- WRQNANDWMGAFTP-UHFFFAOYSA-N Methylacetoacetic acid Chemical compound COC(=O)CC(C)=O WRQNANDWMGAFTP-UHFFFAOYSA-N 0.000 description 5
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
- 229910021529 ammonia Inorganic materials 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 2
- WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 2
- 238000006243 chemical reaction Methods 0.000 description 2
- 150000001875 compounds Chemical class 0.000 description 2
- 239000012043 crude product Substances 0.000 description 2
- 150000007530 organic bases Chemical class 0.000 description 2
- 239000000047 product Substances 0.000 description 2
- 150000003222 pyridines Chemical class 0.000 description 2
- YNGDWRXWKFWCJY-UHFFFAOYSA-N 1,4-Dihydropyridine Chemical compound C1C=CNC=C1 YNGDWRXWKFWCJY-UHFFFAOYSA-N 0.000 description 1
- PLAZTCDQAHEYBI-UHFFFAOYSA-N 2-nitrotoluene Chemical compound CC1=CC=CC=C1[N+]([O-])=O PLAZTCDQAHEYBI-UHFFFAOYSA-N 0.000 description 1
- 206010002383 Angina Pectoris Diseases 0.000 description 1
- 239000002253 acid Substances 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- XGFJCRNRWOXGQM-UHFFFAOYSA-N hot-2 Chemical compound CCSC1=CC(OC)=C(CCNO)C=C1OC XGFJCRNRWOXGQM-UHFFFAOYSA-N 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- HYIMSNHJOBLJNT-UHFFFAOYSA-N nifedipine Chemical compound COC(=O)C1=C(C)NC(C)=C(C(=O)OC)C1C1=CC=CC=C1[N+]([O-])=O HYIMSNHJOBLJNT-UHFFFAOYSA-N 0.000 description 1
- 229960001597 nifedipine Drugs 0.000 description 1
- 230000003647 oxidation Effects 0.000 description 1
- 238000007254 oxidation reaction Methods 0.000 description 1
- 150000002927 oxygen compounds Chemical class 0.000 description 1
- -1 pyridine Chemical compound 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D211/00—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings
- C07D211/04—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D211/80—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members
- C07D211/84—Heterocyclic compounds containing hydrogenated pyridine rings, not condensed with other rings with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having two double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen directly attached to ring carbon atoms
- C07D211/90—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P9/00—Drugs for disorders of the cardiovascular system
- A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Health & Medical Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Urology & Nephrology (AREA)
- Vascular Medicine (AREA)
- Cardiology (AREA)
- Heart & Thoracic Surgery (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Medicinal Chemistry (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Pharmacology & Pharmacy (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Hydrogenated Pyridines (AREA)
Description
Przedmiotem wynalazku jest sposób wytwarzania 4-/21 -nitrofenylo/-2,6-dwukarbometoksy- -1,4-dihydropirydyny o wzorze 1, znanej tez pod" nazwa handlowa Nifedipin i z powodu jej dzia¬ lania rozszerzajacego naczynia wiencowe cenionej jako substancja czynna do leczenia Angina pectoris. 4-/2?-nltrofenylo/-2f6-dwuraetylo-3f5-dwukarbometoksy-1#4-dihydropirydyna jest znana i zostala po raz pierwszy opisana w opisie patentowym RFN nr 1 670 827• Wedlug tamze opisanej metody wytwarza sie zwiazek ten na drodze reakcji 2-nitrobenzaldehydu, acetooctanu metylowego i amoniaku w srodowisku obojetnego rozpuszczalnika organicznego, takiego jak metanol. Metoda ta polega na syntezie pirydyn wedlug Hantzschen/a, gdyz wspomniany ester kwasu 1,4-dihydro- pirydynodwukarboksylowego-3',5 jest trwalym zwiazkiem posrednim, zsyntetyzowanym ta metoda.
Wiadomo, ze niezbedny w tej syntezie zwiazek wyjsciowy, czyli 2-nitrobenzaldehyd, otrzymuje sie droga utleniania 2-nitrotoluenu za pomoca bezwodnika chromowego w obecnosci kwasu siarko¬ wego i bezwodnika octowego /porównaj Houben-Weyl, Methoden der organischen Chemie, tom VII, czesc I, Sauerstoffverbindungen II., 1954, 143/. Zwiazek posredni, czyli dwuacylan 2-hitro- benzaldehydu o wzorze 2, tworzacy sie podczas tej reakcji, Jest substancja trwala, która mozna dalej hydrolizowac do 2-nitrobenzaldehydu. Wydajnosc tej syntezy wynosi okolo 60% wydajnosci teoretycznej.
Nieoczekiwanie stwierdzono, ze dwuacylan 2-nitrobenzaldehydu o wzorze 2 mozna bezposred¬ nio stosowac w syntezie 4-/2'-nitrofenylo/2F6-dwumetylo-3»5-dwukarbometoksy-1,4-dihydropiry- dyny, co oznacza korzystne zastapienie dotychczas stosowanego, drogiego wyjsciowego 2-nitro¬ benzaldehydu przez tanszy omówiono sposobem otrzymywany dwuacalan 2-nitrobenzaldehydu.
Sposób wytwarzania 4-*/2 '-nitrofenylo/2,6-dwumetylo-3,5-dwukarbometoksy-1,4-dihydropiry- dyny o wzorze 1 polega wedlug wynalazku na tym, ze dwuacylan 2-nitrobenzaldehydu o wzorze 2f acetooctan metylowy i amoniak poddaje sie reakcji w obecnosci obojetnego rozpuszczalnika organicznego, takiego Jak metanol, i w obecnosci lub bez obecnosci zasady organicznej, takiej jak pirydynaf w temperaturze 20-150°C. Sposób ten, w którym zaoszczedzono jeden etap2 131 222 syntezy, gdyz zbedna stala sie poprzednio przeprowadzana hydroliza dwuacylenu 2-nltrobenzal dehydu o wzorze 2 do odpowiedniego 2-nitrobenzaldefrydu, stanowi nowa i uproszczona droge syntezy pirydyn wedlug Hantzsch'a.
Podane nizej przyklady objasniaja blizej sposób wedlug wynalazku.
Przyklad I. 0,1 mola /25,4 g/ dwuacylenu 2-nitrobenzaldehydu, 0,2 mola /23,2 g/ acetooctanu metylowego i 12 ml NH OH ogrzewa sie w 20 ml metanolu w obecnosci pirydyny w ciagu 7 godzin. Calosc chlodzi sie do temperatury 15°C, a wytracony produkt odsacza sie. Surowy produkt przekrystalizowuje sie z kwasu octowego, otrzymujac 21,7 g /6296 wydajnosci teoretycznej/ 4-/2'-nitrofenylo/-2,6-dwuinetylo-3,5-dwukarbometoksy-1,4- -dlhydropirydyny o temperaturze topnienia 172-174°C. v Przyklad II. 0,1 aola /25,4 g/ dwuacylenu 2-nitrobenzaldehydu, 2,21 mola /26 g/ acetooctanu metylowego, 12 ml NH.OH i 45 ml metanolu ogrzewa sie w ciagu 5 godzin w temperaturze wrzenia mieszaniny reakcyjnej pod chlodnica zwrotna. Calosc chlodzi sie do temperatury 15°C, a wytracony produkt odsacza sie. Po przekrystalizowaniu surowego produk¬ tu z kwasu octowego otrzymuje sie 19»0 g /55# wydajnosci teoretycznej/ 4-/2 '-nitrofenylo/ -2f6-dwumetylo-3,5-dwukarbometoksy-1,4-dihydropirydyny o temperaturze topnienia 173-174°C.
Z av strzezenie patentowe Sposób wytwarzania 4-/2'-nitrofenylo/2,6dwumetylo-3,5-dwukarbometoksy-1,4-dihydropi- rydyny o wzorze 1, znamienny tym, ze dwuacylan 2-nitrobenzaldehydu o wzorze 2, acetooctan metylowy i amoniak poddaje sie reakcji w obecnosci obojetnego rozpuszczalnika organicznego, takiego jak metanol, i w obecnosci lub bez obecnosci zasady organicznej, N0L C00CH3 i CH (QAc)2 N02 hzot 2 takiej jak pirydyna, w temperaturze 20-150 C.
H3C00C CH^N hfzor & Pracownia Poligraficzna UP PRL. Naklad 100cgz.
Cena 100 zl
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| YU2005/81A YU41983B (en) | 1981-08-19 | 1981-08-19 | Process for preparing 1,4-dihydro-pyridine derivatives |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| PL237935A1 PL237935A1 (en) | 1983-02-28 |
| PL131222B1 true PL131222B1 (en) | 1984-10-31 |
Family
ID=25556467
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| PL1982237935A PL131222B1 (en) | 1981-08-19 | 1982-08-17 | Process for preparing 4-/2'-nitrophenyl/-2,6-dimethyl-3,5-dicarbomethoxy-1,4-dihydropyridine |
Country Status (13)
| Country | Link |
|---|---|
| US (1) | US4467093A (pl) |
| JP (1) | JPS5839663A (pl) |
| AT (1) | AT380876B (pl) |
| CA (1) | CA1185243A (pl) |
| CH (1) | CH651297A5 (pl) |
| DK (1) | DK155734C (pl) |
| ES (1) | ES8306364A1 (pl) |
| FI (1) | FI74275C (pl) |
| NL (1) | NL8203260A (pl) |
| PL (1) | PL131222B1 (pl) |
| SE (1) | SE441743B (pl) |
| SU (1) | SU1099842A3 (pl) |
| YU (1) | YU41983B (pl) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4771057A (en) * | 1986-02-03 | 1988-09-13 | University Of Alberta | Reduced pyridyl derivatives with cardiovascular regulating properties |
| JPH02118009U (pl) * | 1989-03-09 | 1990-09-21 |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1670827C3 (de) * | 1967-03-20 | 1974-10-24 | Bayer Ag, 5090 Leverkusen | 4-(2'-Nitrophenyl)-2,6-dimethyl-3,5-dicarbmethoxy-1,4-dihydropyridin |
| DE2808930A1 (de) * | 1978-03-02 | 1979-09-06 | Bayer Ag | Verfahren zur herstellung von 2-nitrobenzaldehyd |
| JPS554318A (en) * | 1978-06-23 | 1980-01-12 | Asahi Chem Ind Co Ltd | Preparation of 1,4-dihydropyridine |
| JPS5520719A (en) * | 1978-07-31 | 1980-02-14 | Asahi Chem Ind Co Ltd | Preparation of 1,4-dihydropyridine derivative |
| JPS55124760A (en) * | 1979-03-16 | 1980-09-26 | Kanebo Ltd | Preparation of 1,4-dihydropyridine derivative or its salt |
-
1981
- 1981-08-19 YU YU2005/81A patent/YU41983B/xx unknown
-
1982
- 1982-07-27 US US06/402,487 patent/US4467093A/en not_active Expired - Fee Related
- 1982-07-29 CA CA000408333A patent/CA1185243A/en not_active Expired
- 1982-08-11 AT AT0307082A patent/AT380876B/de not_active IP Right Cessation
- 1982-08-11 SE SE8204658A patent/SE441743B/sv not_active IP Right Cessation
- 1982-08-16 FI FI822842A patent/FI74275C/fi not_active IP Right Cessation
- 1982-08-17 PL PL1982237935A patent/PL131222B1/pl unknown
- 1982-08-17 ES ES515063A patent/ES8306364A1/es not_active Expired
- 1982-08-17 CH CH4929/82A patent/CH651297A5/de not_active IP Right Cessation
- 1982-08-18 DK DK370382A patent/DK155734C/da not_active IP Right Cessation
- 1982-08-18 SU SU823482656A patent/SU1099842A3/ru active
- 1982-08-19 JP JP57142768A patent/JPS5839663A/ja active Granted
- 1982-08-19 NL NL8203260A patent/NL8203260A/nl not_active Application Discontinuation
Also Published As
| Publication number | Publication date |
|---|---|
| DK155734B (da) | 1989-05-08 |
| JPS6314709B2 (pl) | 1988-04-01 |
| SE8204658L (sv) | 1983-02-20 |
| US4467093A (en) | 1984-08-21 |
| YU200581A (en) | 1984-02-29 |
| JPS5839663A (ja) | 1983-03-08 |
| SE8204658D0 (sv) | 1982-08-11 |
| FI74275C (fi) | 1988-01-11 |
| PL237935A1 (en) | 1983-02-28 |
| ES515063A0 (es) | 1983-06-01 |
| FI822842L (fi) | 1983-02-20 |
| AT380876B (de) | 1986-07-25 |
| NL8203260A (nl) | 1983-03-16 |
| DK155734C (da) | 1989-09-25 |
| YU41983B (en) | 1988-04-30 |
| ES8306364A1 (es) | 1983-06-01 |
| DK370382A (da) | 1983-02-20 |
| SE441743B (sv) | 1985-11-04 |
| SU1099842A3 (ru) | 1984-06-23 |
| CH651297A5 (de) | 1985-09-13 |
| CA1185243A (en) | 1985-04-09 |
| FI822842A0 (fi) | 1982-08-16 |
| ATA307082A (de) | 1985-12-15 |
| FI74275B (fi) | 1987-09-30 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| IE57715B1 (en) | Asymmetrical diesters of 1,4-dihydro-2,6-dimethyl-pyridine-3,5-dicarboxylic acid | |
| CS418891A3 (en) | Dihydropyridine derivatives, process of their preparation andpharmaceuticals containing said derivatives | |
| CA2178414A1 (en) | Dihydropyridine npy antagonists: nitrogen heterocyclic derivatives | |
| CZ291368B6 (cs) | Způsob a meziprodukty pro přípravu 1H- imidazo[4,5-c]chinolin-4-aminu | |
| JPS6131100B2 (pl) | ||
| KR920005742B1 (ko) | 약제학상 유용한 디하이드로피리디닐디카르복실레이트 아마이드 및 에스테르의 제조방법 | |
| Guzman et al. | Vilsmeier-Haack reaction with glutarimides. Synthesis of 2, 6-dichloro-1, 4-dihydropyridine-3, 5-dicarboxaldehydes | |
| PL131222B1 (en) | Process for preparing 4-/2'-nitrophenyl/-2,6-dimethyl-3,5-dicarbomethoxy-1,4-dihydropyridine | |
| EP1613591B1 (en) | Process to prepare 1,4-dihydropyridine intermediates and derivatives thereof | |
| Şimşek et al. | Synthesis and calcium antagonistic activity of 2, 6, 6-trimethyl-3-carbomethoxy (ethoxy)-4-aryl-1, 4, 5, 6, 7, 8-hexahydroquinoline derivatives | |
| EP0325730B1 (en) | Method for the preparation of O-carboxyarylimindazolinones | |
| JPH0515704B2 (pl) | ||
| EP0142718A1 (en) | Preparation of substituted and unsubstituted 2-((1-carbamoyl-1,2-dimethylpropyl)-carbamoyl)-3-quinolinecarboxylic, nicotinic and benzoic acids | |
| PL159098B1 (en) | Method of obtaining derivatives of 1,4-dihydropyridine | |
| EP0096299B1 (en) | Hydroxyimino and alkoxyimino derivatives of 1,4-dihydropyridine, process for the preparation thereof and pharmaceutical composition therefrom | |
| EP1070053B1 (en) | Synthesis of 3-amino-2-chloro-4-methylpyridine from acetone and ethyl cyanoacetate | |
| US4533735A (en) | Process for preparing antibacterial compounds | |
| JPH0730032B2 (ja) | １−アリ−ル−５−アミノ−ビラゾ−ルの製造方法 | |
| KR100374405B1 (ko) | 암로디핀 베실레이트의 제조방법 | |
| US4550167A (en) | Preparation of 1-alkyl-1,4-dihydro-4-oxo-7-(4-pyridyl)-3-quinoline carboxylic acid | |
| Sagitullina et al. | Nitropyridines. 1. Hantzsch synthesis of nitropyridines and their quaternary salts | |
| JPH0155268B2 (pl) | ||
| Sagitullina et al. | Nitropyridines: IV. Synthesis of 3-(2-furyl) biphenyls by recyclization of nitropyridinium salts | |
| JPS62212368A (ja) | 複素環式化合物の製造 | |
| KR100354806B1 (ko) | 암로디핀 베실레이트의 신규 중간체 및 그의 제조방법 |